tbuckley/cabot-search huggingface dataset:
Abstract IA25: Human genetic studies: CLL and transformation
Authors: Catherine J Wu
Journal: Blood Cancer Discovery (2022)

Abstract Across cancers, histologic transformation remains a major challenge due to its association with rapid tumor progression and resistance. This is well-exemplified by Richter syndrome (RS) – the occurrence of an aggressive lymphoma of dismal prognosis in patients with chronic lymphocytic leukemia (CLL). RS is now a major obstacle to long-term CLL cure since the targeted agents developed for CLL have failed to either prevent or treat RS. In short, RS is becoming a frequent mode of progression and escape through therapeutic resistance. Thus far, definitive evolutionary studies and understanding of the genomic basis of transformation have yet to be completed. Major challenges towards this goal include the very fact that patient biopsy specimens contain an admixture of both CLL and RS tumor cells within the same tumor microenvironment, thereby limiting reliable investigations of RS cells. For CLL, large-scale sequencing studies have successfully demonstrated the diverse spectrum of recurrent gene mutations associated with CLL and the high level of genetic heterogeneity amongst patient samples, consistent with the high degree of clinical variability that is characteristic of this malignancy. We will review new studies to integrate multiple data layers in a cohort of &amp;gt;1000 patients, providing us with a ‘CLL map.’ Recently, we have been developing highly novel analytics that allow us to discern, within a sample that is admixed with both CLL and RS cells, the contributions of CLL vs that of RS. In doing so, we are able to identify new drivers and molecular subtypes of RS, and profile the trajectory from CLL to RS. Such studies are paradigm shifting for the clinic in relationship to both detection, diagnosis and prognosis of RS, and advances our efforts to attain a molecular definition of RS. Moreover, the methodologies, conclusions and detailed studies presented in our work are highly relevant to other hematologic malignancies and solid tumors. Citation Format: Catherine J Wu. Human genetic studies: CLL and transformation [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr IA25.
Beyond Detecting and Understanding Disparities in Novel Diabetes Treatment
Authors: Utibe R. Essien, Donna L. Washington, Michael J. Fine
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Characterization of National Medical Societies’ Accessible Resources to Support Underrepresented Minority and Female Trainees
Authors: Lyndsay A. Kandi, Tyler L. Jarvis, Nellie V. Movtchan, Jacob B. Hammond, Chad M. Teven, Alanna M. Rebecca
Journal: JAMA Network Open (2022)

<h3>Importance</h3> The lack of racial, ethnic, and gender diversity in medicine has been recognized as problematic, but the question of what medical educators and societies are doing to rectify and promote representation of historically marginalized groups persists. <h3>Objective</h3> To examine what easily accessible resources are offered by medical and surgical societies to support women and individuals in minority groups that are underrepresented in medicine (URiM). <h3>Design, Setting, and Participants</h3> This cross-sectional study evaluated transparent and accessible resources on the webpages of societies recognized by the Council of Medical Specialty Societies. Data collection and analysis were performed from September 1, 2021, to November 1, 2021. <h3>Main Outcomes and Measures</h3> The society websites were searched for official diversity statements, diversity and women task forces or committees, and mentorship and scholarship opportunities for URiM and female trainees. The primary outcome was accessible resources in the form of financial support (scholarships) and mentorship for URiM and female trainees. <h3>Results</h3> Of the 45 societies included in the analysis, 38 (84.4%) have published diversity statements. All but 6 societies (86.7%) have a dedicated diversity task force, committee, or work group. Twenty societies (44.4%) have a committee specifically for women or include women in diversity task force initiatives. Seventeen societies (37.8%) offer minority-specific mentorship, 15 (33.3%) offer scholarships targeted toward URiM trainees, 10 (22.2%) provide gender-specific mentorship, and 8 (17.8%) offer scholarship opportunities for female trainees. <h3>Conclusions and Relevance</h3> Although most of the societies included in this study acknowledge the importance of diversity in medicine, less than half of these societies offer readily accessible scholarships or mentorship opportunities to URiM and female applicants.
First Therapy Targeting <i>ERBB2</i>-Low Breast Cancer Approved
Authors: Howard D. Larkin
Journal: JAMA (2022)

The first therapy targeting patients with epidermal growth factor receptor 2 (ERBB2, formerly HER2)–low breast cancer, a newly defined subset of ERBB2-negative breast cancer, gained Food and Drug Administration (FDA) approval, the agency said in a statement.
Abstract IA39: Pathology of AYA lymphomas: Creating a roadmap for translational research
Authors: Megan S. Lim
Journal: Blood Cancer Discovery (2022)

Abstract Mature lymphomas of the adolescent and young adult population (AYA) are rare and clinically and pathobiologically distinct from those in the adult population. The pathobiologic aspects of lymphomas in the AYA population are largely unknown as most studies do not specify age groups and use diagnostic criteria that have been established for lymphomas in the adult population. B-cell lymphomas make up the majority of lymphomas in the AYA population and many are aggressive including Burkitt lymphoma, large/high grade B-cell lymphoma with 11q aberrations and diffuse large B-cell lymphoma (DLBCL), NOS. Most DLBCL, NOS arise as de novo lymphomas. They may occur as a secondary neoplasm after childhood cancer or in cancer predisposition syndromes, primary immunodeficiencies or other inherited genetic diseases (inborn error of immunity-associated lymphoid proliferations and lymphomas). Most DLBCL, NOS in the AYA population are of germinal center derivation, exhibit high proliferation index and while comprehensive studies are lacking, they are biologically distinct from adult diffuse large B-cell lymphomas with less cytogenetic complexity. Mature T-cell lymphomas are extremely rare in the AYA population and composed primarily of those driven by a dominant oncogenic tyrosine kinase (ALK+ anaplastic large cell lymphoma) or Epstein-Barr virus and most arise from T cells of the innate immune system. T-cell lymphomas arising from the adaptive immune system (nodal T follicular helper (TFH) cell lymphoma, peripheral T cell lymphoma, NOS) which are common in the adult population are rare in AYA. The most recent WHO Classification of Paediatric Tumors recognizes specific entities that are enriched in the AYA population with distinct genetic features including indolent B-cell lymphoma including pediatric-type follicular lymphomas, pediatric nodal marginal zone lymphoma and large B-cell lymphomas with IRF4 rearrangement, and EBV-associated T cell lymphoma such as systemic EBV-positive T-cell lymphoma of childhood, systemic chronic active EBV-positive disease and hydroa vacciniforme lymphoproliferative disorder. The distinct clinical and pathobiologic features of lymphomas in the AYA population provide unique opportunities for translational discoveries leveraging innovative technologies such as single cell sequencing, B and T cell immune repertoire analyses and circulating tumor DNA, that will provide insights into the interplay between the immune system, epigenetics, germline predisposition and viruses. These studies are poised to yield actionable information that impacts therapies and improve patient outcomes. Citation Format: Megan S. Lim. Pathology of AYA lymphomas: Creating a roadmap for translational research [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr IA39.
Low CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity
Authors: Xingnan Li, Stefano Guerra, Julie G. Ledford, Monica Kraft, Huashi Li, Annette T. Hastie, Mario Castro, Loren C. Denlinger, Serpil C. Erzurum, John V. Fahy, Benjamin Gaston, Elliot Israel, Nizar N. Jarjour, Bruce D. Levy, David T. Mauger, Wendy C. Moore, Joe Zein, Naftali Kaminski, Sally E. Wenzel, Prescott G. Woodruff, Deborah A. Meyers, Eugene R. Bleecker
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

CC16 is a protein mainly produced by nonciliated bronchial epithelial cells (BECs) that participates in host defense. Reduced CC16 protein concentrations in BAL and serum are associated with asthma susceptibility.
CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018
Authors: Quinn T Ostrom, Mackenzie Price, Katherine Ryan, Jacob Edelson, Corey Neff, Gino Cioffi, Kristin A Waite, Carol Kruchko, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2022)

Abstract The CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and other CNS tumors in children and adolescents ages 0–19 years, collected and reported by central cancer registries covering approximately 100% of the United States population. Overall, brain and other CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in children and adolescents ages 0–19 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.
Uterus Transplant a Clinical Reality
Authors: Anita Slomski
Journal: JAMA (2022)

A report on 5 years of uterus transplant outcomes in the US since the first case in 2016 suggests that the procedure may be a viable way to help some patients with absolute uterine-factor infertility (AUFI) have children. AUFI affects 1 in 500 women.
Benefit of Dapagliflozin When Used With Cardiovascular Medications in Patients With Type 2 Diabetes
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract A21: Novel autochthonous mouse models as preclinical tools in the study of MCD/C5 DLBCL
Authors: Ruth Fluemann, Julia Hansen, Benedikt Pelzer, Tim Lohmann, Ilmars Kisis, Reinhard Büttner, Thorsten Persighel, Nima Abedpour, Martin Peifer, Ron Daniel Jachimowicz, Hans Christian Reinhardt, Gero Knittel
Journal: Blood Cancer Discovery (2022)

Abstract Diffuse large B cell lymphoma (DLBCL) is a clinically and genetically very heterogeneous disease. Several [GK1] [RW2] recent studies attempted to give structure to the genetic heterogeneity by clustering cases based on their mutational profiles. Clusters MCD by Schmitz et al. and C5 by Chapuy et al. are amongst the clusters enriched for cases with particularly inferior prognosis. Both clusters are defined by mutations in MYD88 and CD79B as well as high levels of BCL2 expression and recurring mutations in transcriptional regulators of the plasmacytic differentiation process (PRDM1, SPIB). We have generated genetically-engineered mouse models that mimic key alterations of MCD/C5 DLBCL: Hallmark mutations in MYD88 and CD79B, loss of PRDM1 and overexpression of BCL2/SPIB. We could show that those mice develop clonal lesions, which morphologically resemble DLBCL. In the presence of a lesion that prevents plasmacytic differentiation (overexpression of Spib, loss of Prdm1), the forming lesions display signs of an earlier stage of B cell development, specifically histologic and transcriptomic similarities to germinal center cells. In contrast, allelic combinations without differentiation block lead to lymphomas that express CD138 and lack B220 expression, suggesting a more plasmacytic/plasmablastic differentiation status. The presence or absence of a Cd79b p.Y195H mutation has no notable effect on the immunophenotype of the lymphoma. However, its presence correlates with enrichment of BCR signaling gene set expression in lymphoma tissue and significantly increased sensitivity to inhibition of Bruton’s Tyrosine Kinase (BTK) by ibrutinib in our model systems. Taken together, we have established a set of murine models which mimic different genetic features of C5/MCD DLBCL. We have extensively characterized these models and show their usability as preclinical tools for therapeutic studies. Citation Format: Ruth Fluemann, Julia Hansen, Benedikt Pelzer, Tim Lohmann, Ilmars Kisis, Reinhard Büttner, Thorsten Persighel, Nima Abedpour, Martin Peifer, Ron Daniel Jachimowicz, Hans Christian Reinhardt, Gero Knittel. Novel autochthonous mouse models as preclinical tools in the study of MCD/C5 DLBCL [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr A21.
Audit and Feedback—Optimizing a Strategy to Reduce Low-Value Care
Authors: Deborah Korenstein, Erin F. Gillespie
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Outpatient Care Fragmentation and Acute Care Utilization in Veterans Affairs Home-Based Primary Care
Authors: Samuel T. Edwards, Liberty Greene, Camila Chaudhary, Derek Boothroyd, Bruce Kinosian, Donna M. Zulman
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Veterans Affairs (VA) Home-Based Primary Care (HBPC) provides comprehensive, interdisciplinary primary care at home to patients with complex, chronic, disabling disease, but little is known about care fragmentation patterns and consequences among these patients. <h3>Objective</h3> To examine outpatient care fragmentation patterns and subsequent acute care among HBPC-engaged patients at high risk of hospitalization or death. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included VA patients aged at least 65 years who were enrolled in the VA and Medicare, whose risk of hospitalization or death was in the top 10%, and who had at least 4 outpatient visits between October 1, 2013, and September 30, 2014. HBPC engagement was defined as having at least 2 HBPC encounters between July 1, 2014, and September 30, 2014. Data were analyzed from March 2020 to March 2022. <h3>Exposures</h3> Two indices of outpatient care fragmentation: practitioner count and the Usual Provider Continuity Index (UPC), based on VA and non-VA health care use from October 1, 2013, to September 30, 2014. All care delivered by HBPC clinicians was analyzed as coming from a single practitioner. <h3>Main Outcomes and Measures</h3> Emergency department (ED) visits and hospitalizations for ambulatory care sensitive conditions (ACSC) from VA records and Medicare claims from October 1, 2014, to September 30, 2015. <h3>Results</h3> Among 8908 identified HBPC patients, 8606 (96.6%) were male, 1562 (17.5%) were Black, 249 (2.8%) were Hispanic, 6499 (73.0%) were White, 157 (1.8%) were other race or ethnicity, and 441 (5.0%) had unknown race or ethnicity; the mean (SD) age was 80.0 (9.02) years; patients had a mean (SD) of 11.25 (3.87) chronic conditions, and commonly had disabling conditions such as dementia (38.8% [n = 3457]). In adjusted models, a greater number of practitioners was associated with increased odds of an ED visit (adjusted odds ratio [aOR], 1.05 [95% CI, 1.03-1.07]) and hospitalization for an ACSC (aOR, 1.04 [95% CI, 1.02-1.06]), whereas more concentrated care with a higher UPC was associated with reduced odds of these outcomes (highest vs lowest tertile of UPC: aOR for ED visit, 0.77 [95% CI, 0.67-0.88], aOR for ACSC hospitalization, 0.78 [95% CI, 0.68-0.88]). <h3>Conclusions and Relevance</h3> Among patients in HBPC, fragmented care was associated with more ED visits and ACSC hospitalizations. These findings suggest that consolidating or coordinating fragmented care may be a target for reducing preventable acute care.
Association of Unhealthy Lifestyle and Childhood Adversity With Acceleration of Aging Among UK Biobank Participants
Authors: Gan Yang, Xingqi Cao, Xueqin Li, Jingyun Zhang, Chao Ma, Ning Zhang, Qingyun Lu, Eileen M. Crimmins, Thomas M. Gill, Xi Chen, Zuyun Liu
Journal: JAMA Network Open (2022)

Importance Accelerated aging makes adults more vulnerable to chronic diseases and death. Whether childhood adversity is associated with accelerated aging processes, and to what extent lifestyle mediates the association, remain unknown. Objective To examine the associations of childhood adversity with a phenotypic aging measure and the role of unhealthy lifestyle in mediating these associations. Design, Setting, and Participants A retrospective cohort analysis was conducted using data from adult participants in the UK Biobank baseline survey (2006-2010) and online mental health survey (2016). Data analysis was performed from September 1, 2021, to February 28, 2022. Exposures Childhood adversity, including physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse, was assessed retrospectively through the online mental health survey (2016). Main Outcomes and Measures A phenotypic aging measure, phenotypic age acceleration, was calculated, with higher values indicating accelerated aging. Body mass index, smoking status, alcohol consumption, physical activity, and diet were combined to construct an unhealthy lifestyle score (range, 0-5, with higher scores denoting a more unhealthy lifestyle). Results A total of 127 495 participants aged 40 to 69 years (mean [SD] chronological age at baseline, 56.4 [7.7] years; 70 979 women [55.7%]; 123 987 White participants [97.2%]) were included. Each individual type of childhood adversity and cumulative childhood adversity score were associated with phenotypic age acceleration. For instance, compared with participants who did not experience childhood adversity, those who experienced 4 (β = 0.296, 95% CI, 0.130-0.462) or 5 (β = 0.833; 95% CI, 0.537-1.129) childhood adversities had higher phenotypic age acceleration in fully adjusted models. The formal mediation analysis revealed that unhealthy lifestyle partially mediated the associations of childhood adversity with phenotypic age acceleration by 11.8% to 42.1%. Conclusions and Relevance In this retrospective cohort study, childhood adversity was significantly associated with acceleration of aging and, more importantly, unhealthy lifestyle partially mediated these associations. These findings reveal a pathway from childhood adversity to health in middle and early older adulthood through lifestyle and underscore the potential of more psychological strategies beyond lifestyle interventions to promote healthy aging.